Is ALG9 p.Thr461= (c.1383C>T) pathogenic?

ALG9 p.Thr461= (c.1383C>T) is classified Conflicting classifications of pathogenicity in ALG9 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-06-01). Low-frequency (popmax 1.12%, nfe); Associated with ALG9-congenital disorder of glycosylation.

What condition is associated with ALG9 p.Thr461= (c.1383C>T)?

ALG9 p.Thr461= (c.1383C>T) is associated with ALG9-congenital disorder of glycosylation (ClinVar).

How common is ALG9 p.Thr461= (c.1383C>T) in the general population?

ALG9 p.Thr461= (c.1383C>T) is low-frequency (popmax 1.12%, nfe) (gnomAD).

How is ALG9-CDG inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ALG9 p.Thr461=

c.1383C>T · rs45516107 · VCV380142

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.12%, nfe)

Conditions

ALG9-congenital disorder of glycosylation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.067	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.3	GERP -2.4, phastCons 0.93
Overall
CADD	6.104	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.12% European (non-Finnish) · 13,164/1,180,014 alleles

Filtering AF 1.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.09%

Overall 0.884% 14,266/1,614,154 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.12%	90
Remaining individualsnot grpmax-eligible	0.736%	136
Middle Eastern	0.264%	379
South Asian	0.248%	403
Finnishnot grpmax-eligible	0.228%	439
African / African-American	0.196%	510
Admixed American	0.175%	572
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ALG9
Protein: p.Thr461=
Coding: c.1383C>T
MANE Select: NM_024740
dbSNP: rs45516107
Type: single nucleotide variant
Location: chr11:111837557 (GRCh38)
Gene constraint: LOEUF 0.853 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.35 · 2 PDB

Full ALG9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG9-congenital disorder of glycosylation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For ALG9-CDG (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal

Similar variants

ALG9 p.Thr461Ala Uncertain significance ★ ⚠ same residue
ALG9 p.Thr461Ile Uncertain significance ★ ⚠ same residue
ALG9 c.566-1G>A Pathogenic/Likely pathogenic ★★ same condition
ALG9 c.896-2A>G Likely pathogenic ★★ same condition
ALG9 p.Arg143Ter Pathogenic/Likely pathogenic ★★ same condition
ALG9 p.Trp248Ter Pathogenic/Likely pathogenic ★★ same condition
ALG9 p.Tyr287Cys Pathogenic/Likely pathogenic ★★ same condition
ALG9 c.*1607C>T Uncertain significance ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/alg9-p-thr461 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown